Association ofGSTM1andGSTT1Polymorphism with Lipid Peroxidation in Benign Prostate Hyperplasia and Prostate Cancer: A Pilot Study

Abstract

Association of glutathione S-transferase (GST) M1 and T1 deletions with benign prostate hyperplasia (BPH) and prostate cancer is well reported. These enzymes metabolize numerous toxins thus protecting from oxidative injury. Oxidative stress has been associated with development of BPH and prostate cancer. The present study was designed to analyze role of GST deletions in development of oxidative stress in these subjects. GSTs are responsible for metabolism of toxins present in tobacco therefore effect of tobacco usage in study groups was also studied. Three groups of subjects: BPH (57 patients), prostate cancer (53 patients) and controls (46 subjects) were recruited. Genotyping was done using a multiplex polymerase chain reaction (PCR) method. Malondialdehyde (MDA) levels as marker of oxidative stress were estimated by measuring thiobarbituric acid reactive substance (TBARS) in plasma. Based on genotyping, subjects were categorized into: GSTM1+/GSTT1+, GSTM1-/GSTT1+, GSTM1+/GSTT1- and GSTM1-/GSTT1-. Significantly higher plasma MDA levels were noticed in GSTM1-/GSTT1- as compared to GSTM1+/GSTT1+ in all study groups. Double deletion (GSTM1-/GSTT1-) is associated with higher oxidative stress which might play a role in the pathogenesis of BPH and prostate cancer. However, other markers of oxidative stress should be analyzed before any firm conclusion.

Association of GSTM1 Null Allele with Prostate Cancer Risk: Evidence from 36 Case-Control Studies

“…GSTM1*0 is a deleted allele, and the homozygous allele (GSTM1 null genotype) is thought to be associated with low ability to detoxify several xenobiotics, reduced defense ability against oxidative stress, and free radical-mediated cellular damage [8]–[10]. Many studies on GSTM1 null genotype and PCa have compared the homozygous deletion genotype with the genotypes containing at least one functional allele (Null versus Present) [11]–[44]. Because GSTM1 null genotype could affect PCa risk by mediating the detoxification of activated tobacco carcinogens, it is with great interest that the tobacco smoking might affect the association between GSTM1 null genotype and PCa risk.…”

“…Because GSTM1 null genotype could affect PCa risk by mediating the detoxification of activated tobacco carcinogens, it is with great interest that the tobacco smoking might affect the association between GSTM1 null genotype and PCa risk. Recent years, several studies have evaluated this possible effect [11]–[44]. However, the results are contradictory because of relatively small sample size with low statistical power.…”

GSTT1 and GSTM1 polymorphisms and prostate cancer risk in Asians: a systematic review and meta-analysis

“…Previous studies have suggested that individuals with null genotypes of GSTM1 and GSTT1 may be unable to eliminate electrophilic carcinogens efficiently and suffer from high risk of cancer, and it has been proposed that GSTT1 and GSTM1 polymorphisms are risk factors for prostate cancer. However, the results from previous published studies in Asians reported inconclusive findings [2–4, 18, 19, 26–33]. …”

Significant Association of Glutathione S-Transferase T1 Null Genotype with Prostate Cancer Risk: A Meta-Analysis of 26,393 Subjects

“…Adjusted ORs with corresponding 95%CIs were reported in 13 studies [11]–[13], [26], [28], . There were 7 studies used BPH patients as the controls [10], [12], [17], [18], [29], [35], [51], while only 4 studies used the controls excluding BPH patients [10], [12], [17], [28].…”